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Title: Secretin causes H+/HCO3- secretion from pig pancreatic ductules by vacuolar-type H(+)-adenosine triphosphatase. Author: Villanger O, Veel T, Raeder MG. Journal: Gastroenterology; 1995 Mar; 108(3):850-9. PubMed ID: 7875488. Abstract: BACKGROUND/AIMS: Secretin stimulates pancreatic ductules to secrete HCO3- into pancreatic juice and H+ into interstitial fluid. The aim of the present study was first to examine whether ductular H+ secretion is inhibited by micromolar concentrations of bafilomycin A1, which blocks vacuolar H(+)-adenosine triphosphatase by specific action, and secondly to test for evidence of ductular Na+/HCO3- cotransport. METHODS: Ductular H+ secretion was estimated from the rate of intracellular pH recovery after acid-loading (24 mmol/L NH4Cl) microdissected pancreatic ductules from pig, mounted in a flow-through perfusion chamber on the stage of a fluorescent microscope. Intracellular pH was measured using the fluorescent pH indicator 2'7'-bis (carboxyethyl)-5,6-carboxyfluorescein and dual-wave-length excitation of fluorescence. The ducts were superfused perfused with either HCO3(-)-free HEPES-containing buffers or HCO3(-)-containing buffers. RESULTS: Secretin (10(-8) mol/L) induced a net H+ secretion of 1.87 +/- 0.23 mumol.mL cell vol-1.min-1 that was blocked by 10(-6) mol/L bafilomycin A1 and was unaffected by Na+ substitution with choline using HEPES superfusion buffers. Secretin-stimulated ductules superfused with bicarbonate-containing, Cl(-)-free buffers showed Na(+)-dependent and 4,4'-diisothiocyanostilbene-2, 2'-disulfonic acid-inhibitable alkalinization of intracellular pH. CONCLUSIONS: Secretin causes H+/HCO3- secretion from pancreatic ductules by a mechanism involving vacuolar-type H(+)-adenosine phosphatase. Pancreatic ductules also show Na+/HCO3- cotransport, which may account for a small fraction of secreted bicarbonate.[Abstract] [Full Text] [Related] [New Search]